The physics mechanisms of the weakly coherent mode in the Alcator C-Mod Tokamak

The weakly coherent mode (WCM) in I-mode has been studied by a six-field two-fluid model based on the Braginskii equations under the BOUT++ framework for the first time. The calculations indicate that a tokamak pedestal exhibiting a WCM is linearly unstable to drift Alfven wave (DAW) instabilities and the resistive ballooning mode. The nonlinear simulation shows promising agreement with the experimental measurements of the WCM. The shape of the density spectral and location of the spectral peak of the dominant toroidal number mode n = 20 agrees with the experimental data from reflectometry. The simulated mode propagates in electron diamagnetic direction is consistent with the results from the magnetic probes in the laboratory frame, a large ratio of particle to heat diffusivity is consistent with the distinctive experimental feature of I-mode, and the value of the simulated χeat the edge is in the range of experimental errors of χefffrom the experiment. The prediction of the WCM shows that free energy is mainly provided by the electron pressure gradient, which gives guidance for pursuing future I-mode studies

Radiative heat exhaust in Alcator C-Mod I-mode plasmas

In order to more completely demonstrate the I-mode regime as a compelling fusion reactor operating scenario, the first dedicated attempts at I-mode radiative heat exhaust and detachment were carried out on Alcator C-Mod. Results conclusively show that within the parameter space explored, an I/L back-transition is triggered prior to meaningful reductions in parallel heat flux, q||, target temperature, Te;tar, and target pressure, pe;tar, at the outer divertor. The exact mechanism for the I/L trigger remains uncertain, but a multi-diagnostic investigation suggests the pedestal regulation physics is impacted promptly by small amounts of N2 seeded into the private flux region. The time delay between when N2 contacts the plasma and the I/L transition is triggered varied from 30-120 ms, approximately 0.7-3 x tE, and the delay varied inversely with I-mode pedestal-top pressure, pe;95. Power and nitrogen influx scans indicate that the I/L transitions are not linked to excessive bulk-plasma impurity radiation. It is also shown that in the subsequent L-mode following nitrogen seeding, q|| and Te;tar can be reduced by factors of ~10. The I/L transition and L-mode exhaust results using N2 are compared to similar attempts using Ne where such q|| and Te;tar reductions in L-mode are limited to factors of 2-3. Implications for the I-mode regime are discussed, including needs for follow-up experiments on other facilities

Results of screening in early and advanced thoracic malignancies in the EORTC pan-European SPECTAlung platform.

Access to a comprehensive molecular alteration screening is patchy in Europe and quality of the molecular analysis varies. SPECTAlung was created in 2015 as a pan-European screening platform for patients with thoracic malignancies. Here we report the results of almost 4 years of prospective molecular screening of patients with thoracic malignancies, in terms of quality of the program and molecular alterations identified. Patients with thoracic malignancies at any stage of disease were recruited in SPECTAlung, from June 2015 to May 2019, in 7 different countries. Molecular tumour boards were organised monthly to discuss patients' molecular and clinical profile and possible biomarker-driven treatments, including clinical trial options. FFPE material was collected and analysed for 576 patients with diagnosis of pleural, lung, or thymic malignancies. Ultimately, 539 patients were eligible (93.6%) and 528 patients were assessable (91.7%). The turn-around time for report generation and molecular tumour board was 214 days (median). Targetable molecular alterations were observed in almost 20% of cases, but treatment adaptation was low (3% of patients). SPECTAlung showed the feasibility of a pan-European screening platform. One fifth of the patients had a targetable molecular alteration. Some operational issues were discovered and adapted to improve efficiency

External excitation of a short-wavelength fluctuation in the Alcator C-Mod edge plasma and its relationship to the quasi-coherent mode

A novel “Shoelace” antenna has been used to inductively excite a short-wavelength edge fluctuation in a tokamak boundary layer for the first time. The principal design parameters, k[subscript ⊥] = 1.5 ± 0.1 cm[superscript −1] and 45 < f < 300 kHz, match the Quasi-Coherent Mode (QCM, k[subscript ⊥] ∼ 1.5 cm[superscript −1], f ∼ 50−150 kHz) in Alcator C-Mod, responsible for exhausting impurities in the steady-state, ELM-free Enhanced D[subscript α] H-mode. In H-mode, whether or not there is a QCM, the antenna drives coherent, field-aligned perturbations in density, [˜ over n][subscript e], and field, [˜ over B][subscript θ], which are guided by field lines, propagate in the electron diamagnetic drift direction, and exhibit a weakly damped (γ/ω[subscript 0] ∼ 5%−10%) resonance near the natural QCM frequency. This result is significant, offering the possibility that externally driven modes may be used to enhance particle transport. In L-mode, the antenna drives only a non-resonant [˜ over B][subscript θ] response. The facts that the driven mode has the same wave number and propagation direction as the QCM, and is resonant at the QCM frequency, suggest the antenna may couple to this mode, which we have shown elsewhere to be predominantly drift-mode-like [B. LaBombard et al., Phys. Plasmas 21, 056108 (2014)].United States. Dept. of Energy (Cooperative Agreement DE-FC02-99ER54512

Radial localization of edge modes in Alcator C-Mod pedestals using optical diagnostics

Dedicated experiments in ion cyclotron range heated enhanced D-alpha (EDA) H-mode and I-mode plasmas have been performed on Alcator C-Mod to identify the location of edge fluctuations inside the pedestal and to determine their plasma frame phase velocity. For this purpose, measurements from gas puff imaging (GPI) and gas puff charge exchange recombination spectroscopy (GP-CXRS) have been collected using the same optical views. The data suggest that the EDA H-mode-specific quasi-coherent mode (QCM) is centered near the radial electric field (E r) well minimum and propagates along the ion diamagnetic drift direction in the plasma frame. The weakly coherent mode (WCM) and the geodesic acoustic mode observed in I-mode, on the other hand, are found to be located around the outer shear layer of the E r well. This results in a weak plasma frame phase velocity mostly along the electron diamagnetic drift direction for the WCM. The findings in these EDA H-mode plasmas differ from probe measurements in ohmic EDA H-mode (LaBombard et al 2014 Phys. Plasmas 21 056108), where the QCM was identified as an electron drift-wave located several mm outside the E r well minimum in a region of positive E r. To explore if instrumental effects of the optical diagnostics could be the cause of the difference, a synthetic diagnostic for GPI is introduced. This diagnostic reproduces amplitude ratios and relative radial shifts of the mode profiles determined from poloidally and toroidally oriented optics and, if instrumental effects related to GP-CXRS are also included, indicates that the measured location of the QCM and WCM relative to the E r well reported here is only weakly affected by instrumental effects

EGFR mutations are associated with response to depatux-m in combination with temozolomide and result in a receptor that is hypersensitive to ligand

Background: The randomized phase II INTELLANCE-2/EORTC_1410 trial on EGFR-amplified recurrent glioblastomas showed a trend towards improved overall survival when patients were treated with depatux-m plus temozolomide compared with the control arm of alkylating chemotherapy only. We here performed translational research on material derived from this clinical trial to identify patients that benefit from this treatment.Methods: Targeted DNA-sequencing and whole transcriptome analysis was performed on clinical trial samples. High-throughput, high-content imaging analysis was done to understand the molecular mechanism underlying the survival benefit.Results: We first define the tumor genomic landscape in this well-annotated patient population. We find that tumors harboring EGFR single-nucleotide variations (SNVs) have improved outcome in the depatux-m + TMZ combination arm. Such SNVs are common to the extracellular domain of the receptor and functionally result in a receptor that is hypersensitive to low-affinity EGFR ligands. These hypersensitizing SNVs and the ligand-independent EGFRvIII variant are inversely correlated, indicating two distinct modes of evolution to increase EGFR signaling in glioblastomas. Ligand hypersensitivity can explain the therapeutic efficacy of depatux-m as increased ligand-induced activation will result in increased exposure of the epitope to the antibody-drug conjugate. We also identified tumors harboring mutations sensitive to "classical" EGFR tyrosine-kinase inhibitors, providing a potential alternative treatment strategy.Conclusions: These data can help guide treatment for recurrent glioblastoma patients and increase our understanding into the molecular mechanisms underlying EGFR signaling in these tumors.</p

Memory in low-grade glioma patients treated with radiotherapy or temozolomide: a correlative analysis of EORTC study 22033-26033.

EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time. Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P &lt; 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes. In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy

Evaluation of Best Supportive Care and Systemic Chemotherapy as Treatment Stratified according to the retrospective Peritoneal Surface Disease Severity Score (PSDSS) for Peritoneal Carcinomatosis of Colorectal Origin

Background: We evaluate the long-term survival of patients with peritoneal carcinomatosis (PC) treated with systemic chemotherapy regimens, and the impact of the of the retrospective peritoneal disease severity score (PSDSS) on outcomes. Methods: One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987-2006 were identified from a prospective institutional database. These patients either received no chemotherapy, 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy. Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinically relevant factors. Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test. Results: Median survival was 5 months (95% CI, 3-7 months) for patients who had no chemotherapy, 11 months (95% CI, 6-9 months) for patients treated with 5 FU/LV, and 12 months (95% CI, 4-20 months) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy. Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy (p = 0.026). PSDSS staging was identified as an independent predictor for survival on multivariate analysis [RR 2.8 (95%CI 1.5-5.4); p < 0.001]. Conclusion: A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy. The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin

Determination of chlorinated solvents in industrial water and wastewater by DAI–GC–ECD

A very simple and quick analytical method, based on direct aqueous injection, for determination of halogenated solvents in refinery water and wastewater, is described. There is a need to determine halogenated solvents in refinery water streams, because they may originate from several processes. There is also a need to develop methods enabling VOX to be determined in samples containing oil fractions. The method described enables simultaneous determination of 26 compounds with low detection limits (sub-μg L−1) and excellent precision, especially for highly halogenated solvents. The matrix effects of four types of sample were evaluated—the method seemed to be relatively insensitive to variations in matrix composition. Deuterated 1,2-dichloroethane was used as internal standard and surrogate compound in quantitative analysis; application of isotopically labelled compounds is rarely reported when non-mass spectrometric detectors are used for analysis. Analysis of real samples showed that the most frequently detected compounds were dichloromethane and 1,2-dichloroethane